Proteomic study of human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification

被引:108
作者
Merkel, D [1 ]
Rist, W [1 ]
Seither, P [1 ]
Weith, A [1 ]
Lenter, MC [1 ]
机构
[1] Boehringer Ingelheim Pharma GmbH & Co KG, Proteom Lab, Dept Pulm Res, Genom Grp, D-88397 Biberach, Germany
关键词
bronchoalveolar lavage fluid; chronic obstructive pulmonary disease; mass spectrometry; protein profiling; salivary proline-rich peptides; surface-enhanced laser desorption/ionization;
D O I
10.1002/pmic.200401180
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Bronchoalveolar lavage fluid (BALF) is an important diagnostic source to investigate cellular and molecular changes in the course of lung disorders. The pattern of soluble proteins in BALF obtained from patients at different stages of respiratory disorders may provide deeper insights in the molecular mechanisms of the disease. We used surface-enhanced laser desorption/ionization mass spectrometry (MS) for differential protein display combined with reversed-phase chromatography and subsequent matrix-assisted laser desorption/ionization-MS or nanoliquid chromatography MS/MS analysis for protein identification to compare the protein pattern of BAIT samples obtained from ten smokers suffering from chronic obstructive pulmonary disease (COPD), eight clinically asymptomatic smokers, and eight nonsmokers without pulmonary disease. In this context, we were able to identify small proteins and peptides, either differentially expressed or secreted in the course of COPD or in a direct response to cigarette smoke. The concentrations of neutrophil defensins 1 and 2, S100A8 (calgranulin A), and S100A9 (calgranulin B) were elevated in BALFs of smokers with COPD when compared to asymptomatic smokers. Increased concentrations in S100A8 (Calgranulin A), salivary proline-rich peptide P-C, and lysozyme C were detected in BALFs of asymptomatic smokers when compared to non-smokers, whereas salivary proline-rich peptide P-D and Clara cell phospholipid-binding protein (CC10) were reduced in their concentration. The identified proteins and peptides might be useful in the future as diagnostic markers for smoke-induced lung irritations and COPD.
引用
收藏
页码:2972 / 2980
页数:9
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